OBJECTIVES: This study aimed to assess the factors limiting maximal exercise capacity in patients with chronic heart failure (CHF). BACKGROUND: Maximal exercise capacity, an important index of health in CHF, might be limited by central and/or peripheral factors; however, their contributions remain poorly understood. METHODS: We studied oxygen (O2) transport and metabolism at maximal cycle (centrally taxing) and knee-extensor (KE) (peripherally taxing) exercise in 12 patients with CHF and 8 healthy control subjects in normoxia and hyperoxia (100% O2). RESULTS: Peak oxygen uptake (VO2) while cycling was 33% lower in CHF patients than in control subjects. By experimental design, peak cardiac output was reduced during KE exercise when compared with cycling (approximately 35%); although muscle mass specific peak leg VO2 was increased equally in both groups (approximately 70%), VO2 in the CHF patients was still 28% lower. Hyperoxia increased O2 carriage in all cases but only facilitated a 7% increase in peak leg VO2 in the CHF patients during cycling, the most likely scenario to benefit from increased O2 delivery. Several relationships, peak leg VO2 (KE + cycle) to capillary-fiber-ratio and capillaries around a fiber to mitochondrial volume, were similar in both groups (r = 0.6-0.7). CONCLUSIONS: Multiple independent observations, including a significant skeletal muscle metabolic reserve, suggest skeletal muscle per se contributes minimally to limiting maximal cycle exercise in CHF or healthy control subjects. However, the consistent attenuation of the convective and diffusive components of O2 transport (25% to 30%) in patients with CHF during both cycle and even KE exercise compared with control subjects reveals an underlying peripheral O2 transport limitation from blood to skeletal muscle in this pathology.